Parental exposure to tris(1,3-dichloro-2-propyl) phosphate results in thyroid endocrine disruption and inhibition of growth in zebrafish offspring

Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a re-emerging environmental contaminant used as a suitable substitute for brominated flame retardants. The objective of this study was to evaluate the effects of TDCIPP on thyroid disruption and growth inhibition in zebrafish (Danio rerio) offspring after chronic parental exposure, and to examine the possible molecular mechanisms involved. When adult zebrafish (4 months old) were exposed to 5.66, 25.55, or 92.8 mu g TDCIPP/L for 90 days, bioconcentration of TDCIPP and its metabolic product [bis(1,3-dichloro-2-propyl) phosphate, BDCIPP] was observed in 7-day postfertilization (dpf) F1 larvae, which suggests the transfer of this compound from adult fish to their offspring. Our results demonstrated that parental exposure to TDCIPP induced thyroid disruption in the offspring, demonstrated by significantly decreased thyroxine (T4) and increased 3,5,3'-triiodothyronine (T3) levels, and disruption of the transcription of several genes and expression of proteins involved in the hypothalamic-pituitary-thyroid (HPT) axis in F1 larvae. Parental exposure to TDCIPP resulted in developmental abnormalities in offspring; the smaller body length that was recorded might be partly the result of the perturbation of the HPT axis. In addition, the results revealed that growth inhibition also resulted from the downregulation of the transcription of genes and expression of proteins involved in the growth hormone/insulin-like growth factor (GH/IGF) axis. Our study provides a new set of evidence showing that parental exposure to TDCIPP can induce thyroid disruption and inhibition of growth in offspring, and that perturbation of the HPT axis and GH/IGF axis contribute to these adverse effects.